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@ARTICLE{Sturm:274348,
author = {D. Sturm$^*$ and D. Capper$^*$ and F. Andreiuolo and M.
Gessi and C. Kölsche and A. Reinhardt and P. Sievers and A.
K. Wefers and A. Ebrahimi$^*$ and A. K. Suwala$^*$ and G. H.
Gielen and M. Sill$^*$ and D. Schrimpf and D. Stichel$^*$
and V. Hovestadt and B. Daenekas and A. Rode$^*$ and S.
Hamelmann$^*$ and C. Previti$^*$ and N. Jäger$^*$ and I.
Buchhalter$^*$ and M. Blattner-Johnson$^*$ and B. C.
Jones$^*$ and M. Warmuth-Metz and B. Bison and K. Grund and
C. Sutter and S. Hirsch$^*$ and N. Dikow and M. Hasselblatt
and U. Schüller and N. U. Gerber and C. L. White and M. K.
Buntine and K. Kinross and E. M. Algar and J. R. Hansford
and N. G. Gottardo and P. Hernáiz Driever and A. Gnekow and
O. Witt$^*$ and H. L. Müller and G. Calaminus and G.
Fleischhack and U. Kordes and M. Mynarek and S. Rutkowski
and M. C. Frühwald and C. M. Kramm and A. von Deimling$^*$
and T. Pietsch and F. Sahm$^*$ and S. M. Pfister$^*$ and D.
Jones$^*$},
title = {{M}ultiomic neuropathology improves diagnostic accuracy in
pediatric neuro-oncology.},
journal = {Nature medicine},
volume = {29},
number = {4},
issn = {1078-8956},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DKFZ-2023-00550},
pages = {917-926},
year = {2023},
note = {#EA:B360#LA:B300#LA:B062#LA:B360# / 2023 Apr;29(4):917-926},
abstract = {The large diversity of central nervous system (CNS) tumor
types in children and adolescents results in disparate
patient outcomes and renders accurate diagnosis challenging.
In this study, we prospectively integrated DNA methylation
profiling and targeted gene panel sequencing with blinded
neuropathological reference diagnostics for a
population-based cohort of more than 1,200 newly diagnosed
pediatric patients with CNS tumors, to assess their utility
in routine neuropathology. We show that the multi-omic
integration increased diagnostic accuracy in a substantial
proportion of patients through annotation to a refining DNA
methylation class $(50\%),$ detection of diagnostic or
therapeutically relevant genetic alterations $(47\%)$ or
identification of cancer predisposition syndromes $(10\%).$
Discrepant results by neuropathological WHO-based and DNA
methylation-based classification $(30\%)$ were enriched in
histological high-grade gliomas, implicating relevance for
current clinical patient management in $5\%$ of all
patients. Follow-up (median 2.5 years) suggests improved
survival for patients with histological high-grade gliomas
displaying lower-grade molecular profiles. These results
provide preliminary evidence of the utility of integrating
multi-omics in neuropathology for pediatric neuro-oncology.},
cin = {B360 / BE01 / B300 / B062 / W610 / B310 / HD01},
ddc = {610},
cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)BE01-20160331 /
I:(DE-He78)B300-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)W610-20160331 / I:(DE-He78)B310-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36928815},
doi = {10.1038/s41591-023-02255-1},
url = {https://inrepo02.dkfz.de/record/274348},
}